tbuckley/cabot-search huggingface dataset:
Camrelizumab in combination with fluorouracil or taxol plus platinum chemotherapy as first-line treatment of esophageal squamous cell carcinoma: A multicenter, open-label, prospective cohort study.
Authors: Jun Zhao, Wenqing Hu, Xiaoling Zhang, Yunyi Du, Chunmei Yao, Ning Ma, Wei Yang, Bo Yang, Yudong Xue, Yangjun Gao, Yu Wang, Min Liu, Mei Wang, Hui Wang, Tingting Feng, Linlin Cai, Cuihua Zhang, Kai Ma, Ning Xu, Jing Lu
Journal: Journal of Clinical Oncology (2022)

e16084 Background: The introduction of immune checkpoint inhibitors (ICIs) after chemotherapy and targeted therapy has altered the treatment pattern of esophageal squamous cell carcinoma (ESCC). However, using ICIs alone results in a poor response rate. Fortunately, fundamental research indicates that chemotherapy might trigger immunogenic death of tumor cells by releasing tumor antigens, hence eliminating immune system repression of tumor cells. On this basis, a number of clinical studies, including KEYNOTE-590, CheckmMate-648, ORIENT-15, and ESCORT-1st, on the first-line treatment of ESCC with ICIs coupled with chemotherapy, including fluorouracil or taxol and platinum (PF or TP), were conducted and yielded favorable results. However, the advantage of safety and effectiveness of ICIs combination with PF and TP in Chinese ESCC remains unknown. Furthermore, since the southeast part of Shanxi province has a high prevalence of esophageal cancer, the geographical features of ESCC patients will be examined. Methods: Camrelizumab was maintained after 6 cycles of camrelizumab in combination with PF or TP chemotherapy. From May 2020 to February 2022, our study has included 40 locally progressed and advanced ESCC patients. Camrelizumab was administered in combination with PF to 11 patients and TP to 29 patients. Every 6 weeks, efficacy was examined using RECIST 1.1, and 33 patients were evaluated. This research was registered with the Chinese Clinical Trials Registry (ChiCTR2000037942). Results: The median treatment time was 5.8m. 82.5% (33/40) patients were availably evaluated. The objective response rate (ORR) was 72.7% (24/33) and the disease control rate (DCR) was 97.0% (32/33). There is no statistically significant difference in ORR ( p=0.1779) and DCR ( p=0.1005) between PF and TP (55.6% vs 79.2%, 88.9% vs 100%) regimens. At this moment, mPFS has not been achieved. The most common adverse events (AEs) were anemia (22.5%, 9/40), lymphocytopenia (15%, 6/40), neutropenia(15%, 6/40), reactive cutaneous capillary endothelial proliferation (RCCEP) (12.5%, 5/40) and fatigue (7.5%, 3/40). Thrombocytopenia (2.5%, 1/40), neutropenia (2.5%, 1/40) and leukopenia (2.5%, 1/40) were the most common grade 3 or 4 toxicities The most frequently reported immune-related AEs were RCCEP (12.5%, 5/40) and hypothyroidism (7.5%, 3/40). There were no new significant adverse events. Conclusions: Camrelizumab in combination with chemotherapy is a promising regimen with good tolerability in the first-line treatment of ESCC. Compared with FP, TP had more therapeutic advantages, But the result is a stage summary, and further observation is needed. Clinical trial information: ChiCTR2000037942. [Table: see text]
Long-term toxicity and tolerance of concurrent docetaxel with radiotherapy in cisplatin ineligible head and neck cancer patients.
Authors: Manali Kolkur, Vijay Maruti Patil, Nandini Sharrel Menon, Vanita Noronha, Kumar Prabhash, Vijai Simha, Vikas Talreja, Arun Chandrasekharan, Sachin Dhumal
Journal: Journal of Clinical Oncology (2022)

e18037 Background: Docetaxel can be administered in several situations like low creatinine clearance or pre-existing grade 3-4 ototoxicity, where cisplatin is contraindicated. In this analysis, we present our data on toxicity and tolerance to docetaxel-based chemoradiation in cisplatin-ineligible patients. Methods: Patients who underwent docetaxel-based chemoradiation between January 2015 to December 2017 for locally advanced head and neck cancer, either in the radical or adjuvant setting were selected for this analysis. SPSS version 16 was used for analysis. Results: Nineteen patients were identified and the median age of the cohort was 58 years (range 41-71 years). The most common site of the primary was the oral cavity (n = 9, 47.4%). Sixteen patients (84.2%) had stage IV disease and 3 patients (15.8%) had stage 3 disease. The intent of chemoradiation was radical in 12 (63.9%) patients and adjuvant in 7 (36.1%) patients. Any grade 3 or above adverse events were seen in 12 patients (63.2%). The most common grade 3 or above adverse events observed were mucositis and hyponatremia in 9 patients (47.4%) each. At a median follow up of 5.3 years, the 2-year and 5-year PFS were 26.3% (Standard error-10.1) and 15.8% (Standard error- 8.4) while 2-year and 5-year OS were 36.8% (Standard error-11.1) and 15.8% (Standard error- 8.4). Conclusions: Docetaxel based chemoradiation is a feasible and tolerated option in cisplatin unfit patients and needs further testing in large randomized studies to prove its worth.
Uses of GFR and Albuminuria Level in Acute and Chronic Kidney Disease
Authors: Andrew S. Levey, Morgan E. Grams, Lesley A. Inker
Journal: New England Journal of Medicine (2022)

Testing for kidney disease is routine in clinical practice. This review focuses on advances in clinical evaluation of the glomerular filtration rate and albuminuria and their use in detecting acute and chronic kidney disease, designing trials of disease progression, and predicting risk in clinical practice.
Platinum-free chemotherapy in the new era of immunotherapy: A phase II study of camrelizumab combined with apatinib and albumin paclitaxel in advanced non-squamous NSCLC (CAPAP-lung).
Authors: Lin Wu, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, bolin chen, Xiaoping Wen, Yali Tan
Journal: Journal of Clinical Oncology (2022)

9034 Background: Cytotoxic chemotherapy and anti-angiogenic therapy may enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Platinum-containing dual-agent chemotherapy combined with ICIs is the standard first-line treatment for non-small cell lung cancer (NSCLC), however, the optimal combination regimen remains unclear. The adverse effects of platinum-based chemotherapy are relatively serious, whether platinum chemotherapy can be eliminated in the first-line treatment of non-small cell lung cancer is a hotspot and difficulty in current research. Based on these results, we initiated CAPAP-lung study, which is a single-arm, multicenter Phase II trial to evaluate the efficacy and safety of Camrelizumab in combination with apatinib and albumin paclitaxel without platinum as the first-line therapy for non-squamous non-small cell lung cancer. Methods: Patients diagnosed with ⅢB-IV non-squamous NSCLC without EGFR and ALK sensitive mutations received Camrelizumab (200mg/3w) in combination with Albumin Paclitacxel (135mg/m 2 , d1, d8/3w, 4-6 cycles) and Apatinib (250mg Qd po for 5 days, resting for 2 days every week). From August 2020 to February 2022, 54 of the planned 63 patients have been enrolled. The primary endpoint is progression-free survival(PFS), and secondary endpoints were overall survival (OS), duration of Response (DOR), objective response rate (ORR), and disease control rate (DCR) assessed by RECIST v1.1. This study is registered with ClinicalTrials.gov, NCT04459078 (follow-up is ongoing). Results: The data for a total of 38 patients out of 54 enrolled patients were evaluable. Median PFS was 10.97 mo (95%CI 7.1-NR).The objective response rate (ORR) and disease control rate (DCR) were 71.1% (27/38, 95%CI 53.9-84.0) and 97.4% (37/38, 95%CI 84.6-99.9), respectively. The incidence of grade 3 and worse treatment-related adverse events was acceptable, with grade 3 events in 25(46.3%) patients and grade 4 events in 3(5.6%) patients. The most common grade 3 treatment-related adverse events were decreased neutrophil count (8 [14.8%]), liver function damage (9 [16.7%]), rash (3 [5.6%]), and decreased white blood cell count (3 [5.6%]). Conclusions: Camrelizumab combined with albumin paclitaxel and apatinib showed encouraging antitumor activity with an acceptable safety profile for the first-line treatment of advanced lung adenocarcinoma. Clinical trial information: NCT04459078.
Exploring the mechanism of PARPi resistance in ovarian cancer by integrated analyze of pre- and post-progression samples in 5 patients.
Authors: Qingli Li, Liang Song, Xiaojuan Lin, Wenhao Zhang, Peng Cheng, Changbin Zhu, Rutie Yin
Journal: Journal of Clinical Oncology (2022)

e17582 Background: PARP inhibitors (PARPi) have been widely used in the treatment of homologous recombination repair-deficient tumors. Comprehensive investigations on the resistance mechanisms of PARPi and tumor microenvironment alterations after PARPi therapy are largely insufficient. Methods: 5 ovarian cancer patients (pts) treated with PARPi at West China Second University Hospital were enrolled in this study (Ethical Lot Number: 20200076). Clinicopathological information of the pts are shown in table below. Paired PARPi treatment-naive surgical samples (TNS) and the biopsy samples that progressed after PARPi maintenance therapy (PPS) were obtained. Multi-omic profiling was conducted by an NGS panel (Master Panel, AmoyDx) containing DNA exon regions of 563 genes and RNA expression of 1831 genes analyzing genetic mutations and dynamics of gene expression profile in these paired tumor samples. Results: Median duration of treatment with PARPi was 18 months (11-22). Comprehensive genomic profiling discovered MYC amplification (n = 3), ZFHX4 mutation (n = 2) and IDH1 mutation (n = 1) in PPS. One PPS harbored simultaneous amplification of PDCD1, FGF3, MYC, FGF19 and ZFHX4 mutation. In addition, BRCA1 intron11: c.4096+1G &gt; T mutation was detected in one PPS carrying germline BRCA1 mutation (E1066*), which putatively resulted in restoration of BRCA1 function. At RNA level, single-sample enrichment analysis showed that B cells, T cells, and co-activation factors were significantly up-regulated in PPS. In addition, expression of CXCL13 and activation of CCL19/21-CCR7 axis were significantly increased, which indicated a PARPi-triggered “hot” immune-microenvironment. Moreover, immune-checkpoint TIGIT was significantly upregulated, paved the way for immunotherapy. Nevertheless, stromal remodeling, and tumor proliferation signatures were also up-regulated in PPS. In parallel, cancer-related pathways, PI3K/AKT, Epithelial-Mesenchymal transition, cell-cycle as well as G2M checkpoint were observed in the pathway enrichment analysis, which further verified the aforementioned findings. Conclusions: This small sample size study confirmed the complexity of the resistance mechanisms to PARPi, including BRCA reversion mutation, oncogene activation and bypass signaling activation. The activation of both positive and negative immune regulators in the tumor microenvironment shed light on future clinical management for patients with PARPi resistance.[Table: see text]
Characterizing malignant transformation in patients with <i>IDH-</i>mutant glioma.
Authors: Vicki Liu, Blaine S.C. Eldred, Ethan Wetzel, Serendipity Zapanta Rinonos, Negar Khanlou, Linda M. Liau, Phioanh Leia Nghiemphu, Timothy Francis Cloughesy, Benjamin M. Ellingson, Albert Lai
Journal: Journal of Clinical Oncology (2022)

2065 Background: Gliomas, which constitute the majority of primary brain cancers in adults, are assigned to a particular grade based on histological and molecular criteria set forth by the World Health Organization (WHO). A subset of initially low grade glioma patients transition to a higher grade at recurrence through a process known as malignant transformation (MT). Despite its significant implications on clinical prognosis, MT remains a poorly understood phenomenon in regards to its incidence rates, effects on survival, and potential prognostic factors. Our study aims to elucidate MT in patients that possess a mutation in the isocitrate dehydrogenase ( IDH) gene, one of the most common genetic alterations in gliomas. Methods: All known IDH mutant glioma patients, seen at UCLA between 1986 and 2022, who received at least 1 repeat resection for presumed recurrent disease were included. Based on surgical pathology reports, patients were categorized into MT and non-transforming progression groups, and further stratified by diagnosis in compliance with the 2016 WHO Classification of Tumors of the Central Nervous System. Relevant clinical information, including patient demographics, survival data, tumor microscopic descriptions, and magnetic resonance imaging, was accessed via electronic medical records. Kaplan Meier analyses were conducted to evaluate the predictive power of various clinical, pathological, and radiological markers. Results: Of 724 total IDH mutant patients screened, 253 received a second surgery and were thus incorporated in this study. Among the 196 patients with lower grade pathologies capable of MT, 129 (65.8%) progressed to a higher grade at recurrence while 71 (36.2%) did not. By diagnosis, the incidence rates of MT for initial grade 2 astrocytomas, grade 3 astrocytomas, and grade 2 oligodendrogliomas were determined to be 74.7%, 48.9%, and 66.1%, respectively. MT was associated with worse overall survival and post-recurrence survival compared to non-transformation in astrocytomas, a trend not seen in oligodendrogliomas. Across all relevant diagnoses, a subset of 36 MT patients did not receive treatment in the interval between initial and recurrent surgery, demonstrating the existence of spontaneously occurring MT. Furthermore, consolidating data from pathology and MRI reports revealed that a greater extent of abnormal molecular characteristics at initial diagnosis and earlier post-operative contrast enhancement may predict MT. Conclusions: These results highlight the distinct nature of gliomas that undergo MT, particularly in tumors of astrocytic differentiation. Considering its adverse impact on clinical outcome, understanding and anticipating this phenomenon is instrumental for the determination of optimal treatment among glioma patients.
Initial clinical results of the first commercial clinical blood test dedicated to the early detection of pancreatic ductal adenocarcinoma (PDAC).
Authors: Thomas C. King
Journal: Journal of Clinical Oncology (2022)

e16258 Background: The IMMray® PanCan-d blood test for early detection of PDAC has been commercially available in 45 U.S. states since the laboratory’s licensure in August 2021. This is the first clinically-available blood test dedicated to the early detection of PDAC, combining an 8-plex biomarker signature with CA19-9 in a proprietary algorithm. Here we report the initial results of this assay. Methods: All orders received and results reported were reviewed for the IMMray PanCan-d test between August 4, 2021 and February 11, 2022. Serum specimens were processed at the Immunovia, Inc. laboratory in Marlborough, Massachusetts. Demographic information of individuals undergoing testing is based on the completed test requisition submitted by their health care providers. All information was de-identified prior to this analysis. Results: The median age of those tested was 59 years and 46% were male. 76% of patients were referred because of a history of familial pancreatic cancer. Germline mutation prevalence is reported in the table below. 12% of patients had IPMNs or mucinous cystic neoplasms, 2% had chronic pancreatitis and 3% had new onset Diabetes Mellitus. Table. Demographics of Individuals Tested with the IMMray PanCan-d test 80.5% of IMMray PanCan-d results were negative, 1.1% were high-risk signature present, and 11.5% were borderline. These results are fully consistent with validation studies for this assay in high-risk surveillance populations (Brand RE et al Clin Transl Gastroenterol, doi: 10.14309/ctg.0000000000000468). 6.9% of individuals tested had a CA19-9 value of less than 2.5 U/ml, which we identify as presumptively Lewis null (le/le) and CA19-9 non-secretors. Given that CA19-9 contributes significantly to calculated decision values for the IMMray PanCan-d test, individuals with a CA19-9 less than 2.5 U/ml receive a result of test not performed. Conclusions: The commercial availability of a biomarker assay for the early detection of PDAC resulted in a testing population with demographics and referral criteria similar to that of PDAC high-risk surveillance programs in the U.S. IMMray PanCan-d test results were as expected based on prior validation studies.[Table: see text]
QOL-10. Treatment-induced leukoencephalopathy in pediatric medulloblastoma survivors and its impact on long-term neurocognitive functioning
Authors: Lukas Wägner, Brigitte Bison, Anne Neumann-Holbeck, Tanja Tischler, Anika Guiard, Denise Obrecht, Holger Ottensmeier, Rolf-Dieter Kortmann, Katja von Hoff, Paul-Gerhardt Schlegel, Marc Remke, Antje Redlich, Ursula Holzer, Claudia Blattmann, Gudrun Fleischhack, Annette Sander, Norbert Jorch, Martina Becker, Michael Karremann, Michael C Frühwald, Miriam van Buiren, Nina Struve, Monika Warmuth-Metz, Stefan Rutkowski, Martin Mynarek
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVES: Leukoencephalopathy (LEP, i.e. white matter T2-/FLAIR-hyperintensities on MRI) and impaired neuropsychological outcome are side effects of multimodal therapy of medulloblastoma. We identified risk factors for LEP and correlated LEP with neurocognitive functioning. PATIENTS AND METHODS: Severity of LEP either at the end of therapy (n=118), two years (n=126), or five years after surgery (n=139) was evaluated according to an adapted Fazekas classification for 162 survivors of medulloblastoma (median age: 7.4 years [range:0.67-19.8 years]). Severity of LEP two or five years after surgery was correlated with treatment and neurocognitive functioning ≥ five years after diagnosis using univariate analyses and multivariate generalized mixed linear models. RESULTS: Two and five years after surgery, incidences of mild/moderate/severe LEP were 21.4%/17.5%/9.5%, and 24.5%/23.7%/8.6%, respectively. Data on severity of LEP both at the end of therapy and five years after surgery was available for 103 patients: LEP grades increased for 1/2 degrees in 18/4 patients and decreased in 13/1 patients, respectively. Both treatment approaches - HIT-SKK chemotherapy including intraventricular methotrexate (SKK) and craniospinal irradiation (CSI) - were associated with increased severity of LEP (CSI+SKK &amp;gt; SKK only &amp;gt; CSI only; p&amp;lt;0.001). Severe LEP only occurred in patients treated with both CSI and SKK. In total 19% of all patients treated with this combination developed severe LEP. Severe LEP correlated with impaired fluid (p=0.013) and crystalline (p=0.012) intelligence and short-term memory (p=0.024) on both univariate level and in multivariate mixed linear models. Among patients treated with CSI doses &amp;gt;30Gy, severe LEP, but not SKK including intraventricular MTX, correlated with impaired neurocognitive functioning. CONCLUSION: After therapy strong changes in LEP rarely occurred. Severe LEP was associated both with the combination of SKK and CSI, and impaired neurocognitive functioning. Further research will be needed to weigh potential benefits of SKK including intraventricular methotrexate with CSI against its neurotoxicity.
Robot-assisted Mitrofanoff appendicovesicostomy
Authors: C. Haudebert, J. Hascoet, P-E. Bryckaert, L. Freton, C. Richard, Z-E. Khene, C. Voiry, E. Samson, R. Mathieu, G. Verhoest, K. Bensalah, A. Manunta, B. Peyronnet
Journal: European Urology (2022)
Cow's milk and egg protein threshold dose distributions in children tolerant to beef, baked milk, and baked egg
Authors: Rocco Luigi Valluzzi, Carla Riccardi, Stefania Arasi, Anna Lucia Piscitelli, Veronica Calandrelli, Lamia Dahdah, Vincenzo Fierro, Maurizio Mennini, Alessandro Fiocchi
Journal: Allergy (2022)

The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing oral food challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) is 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children.We retrospectively assessed consecutive OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children.Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 was 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 was 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are, respectively, 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds.The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared with milk in the determinism of fatal anaphylactic reactions in children.